In recent years, the popularity of hydrophilic interaction chromatography (HILIC) in the analysis of small polar and ionizable molecules increased substantially. A large number of new stationary phases with sub-2-micro m and superficially porous particles were developed and used in various applications, including pharmaceuticals, metabolites, biomarkers, amino acids and peptides.
Applications of HILIC in ultra-high performance liquid chromatography (UHPLC) mode constitute only about 10% of all current HILIC applications. This review presents an overview of UHPLC in HILIC mode, including the importance of the final sample diluent, a discussion on available stationary phases and approaches to detection, and a comparison of performance with other chromatographic modes.